Attenuation of PTZ Induced Generalized Clonic and Myoclonic Seizures by Meloxicam

Authors

  • Kalpana Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Ziauddin University Karachi.
  • Sayyed Mudasar Hussain Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Ziauddin University Karachi.
  • Uzair Nisar Department of Pharmacology, Faculty of Pharmacy and Pharmaceutical Sciences, Ziauddin University Karachi.
  • Md. Jamal Department of Pharmacy, City University of Science and Information Technology, Peshawar, Pakistan.
  • Shabana Usman Simjee H.E.J. Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan

Keywords:

Epilepsy, Pentylenetetrazol (PTZ), Meloxicam, Neuroinflammation, COX-2 inhibitor, Seizure model, Neuroprotection

Abstract

Background: Millions of people worldwide suffer from epilepsy, a condition marked by repeated seizures, with about one-third of patients not being well controlled by the antiepileptic medications now on the market. In experimental settings, the Pentylenetetrazol (PTZ) model is frequently employed to cause seizures, offering a framework for assessing possible therapies. Since inflammation is a key factor in the epilepsy etiology, nonsteroidal anti-inflammatory medications (NSAIDs) with specific COX-2 inhibitors like meloxicam may have neuroprotective effects.

Objective: To evaluate meloxicam's anticonvulsant qualities in a mouse model of PTZ-induced seizures is the main aim of this study.

Materials & Methods: Five groups of male NAVAL MEDICAL RESEARCH INSTITUTE(NMRI) mice were established: control, diazepam + PTZ, meloxicam (25 mg/kg) + PTZ, meloxicam (15mg/kg) + PTZ, and PTZ only. Tukey and ANOVA's post-hoc test were used for the statistical analysis of the observed parameters for seizure onset, duration, severity, and post-seizure outcomes.

Results: When compared to the PTZ-only group, meloxicam exhibited improved survival rates, decreased seizure length and severity, and markedly delayed the start of the first myoclonic jerk and generalized seizures. With a 90% survival rate, the high-dose meloxicam group (15 mg/kg) showed the most noticeable effects.

Discussion: In the acute PTZ model, meloxicam significantly reduced the occurrence of generalized clonic and myoclonic seizures, indicating its potent anticonvulsant effects. This outcome is likely due to meloxicam’s COX-2 inhibition and TgF beta inhibition, which reduces the neuroinflammation and stabilizes neuronal excitability. By lowering pro-inflammatory prostaglandins that contribute to seizure susceptibility, meloxicam not only modulates seizure activity but may also offer neuroprotective benefits. These findings suggest meloxicam’s potential as a therapeutic option in epilepsy.

Conclusion: Meloxicam has demonstrated potential as an anticonvulsant medication in PTZ-induced seizures, indicating the need for additional research into its long-term effectiveness and procedures of action in the epilepsy’streatment.

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Published

2025-01-09